EFFECTOR T-LYMPHOCYTE SUBSETS IN HUMAN PANCREATIC-CANCER - DETECTION OF CD8(-EPITOPE IMAGING() CD18(+) CELLS AND CD8(+) CD103(+) CELLS BY MULTI)

Pancreatic cancer is characterized by an increasing incidence and an e xtremely poor prognosis. It is resistant to most of the conventional t reatment modalities. Histomorphologically, it presents with a strong d esmoplastic reaction around cancer cells, and lymphocytes are typicall y localized as aggregates in the fibrotic interstitial tissue. Using t he method of multi-epitope imaging with fluorochrome-tagged specific M oAbs which allows the simultaneous localization and characterization o f T cells in tissues, we studied phenotypes and distribution of tumour -infiltrating lymphocytes (TIL) in pancreatic cancer. CD3(+) T cells c omprised up to 90% of the tumour-infiltrating cells which were either CD4(+) or CD8(+) most of them being memory cells (CD45RO(+)). In decre asing order of frequency, T lymphocytes carried the markers for CD45RO , CD18, CD103 and TCR gamma delta. Very few natural killer cells (CD56 (+)) were observed. Twenty percent of CD8(+) were labelled with CD103. These CD8(+) CD103(+) T cells, analogous to the gut intraepithelial l ymphocytes (IEL), were found in the fibrous interstitial tissue. Furth ermore, an inverse correlation was found between the expression of CD1 8, the beta(2)-integrin, which mediates adhesion of activated lymphocy tes, and CD45RO in the CD8(+) subset of TIL (P = 0.046). In conclusion , phenotyping of T lymphocytes in pancreatic cancer raises the possibi lity that pancreatic cancer cells develop several strategies to escape the T cell-induced cytolysis by (i) the aggregation of cytotoxic CD8( +) CD103(+) T cells in the fibrous tissue distant from the tumour cell s, and (ii) the presence of CD18-bearing cells which lack the expressi on of the activation marker CD45RO.